The release of GLP-1 and ghrelin, but not GIP and CCK, by glucose is dependent upon the length of small intestine exposed

Abstract

Previous observations suggest that glucagon-like peptide-1 (GLP-1) is released into the bloodstream only when dietary carbohydrate enters the duodenum at rates that exceed the absorptive capacity of the proximal small intestine to contact GLP-1 bearing mucosa in more distal bowel. The aims of this study were to determine the effects of modifying the length of small intestine exposed to glucose on plasma concentrations of GLP-1 and also glucose-dependent insulinotropic peptide (GIP), insulin, cholecystokinin (CCK) and ghrelin, and antropyloric pressures. Glucose was infused at 3.5 kcal/min into the duodenum of eight healthy males (age 18 -59 yr) over 60 min on the first day into an isolated 60-cm segment of the proximal small intestine ("shortsegment infusion"); on the second day, the same amount of glucose was infused with access to the entire small intestine ("long-segment infusion"). Plasma GLP-1 increased and ghrelin decreased (P Ͻ 0.05 for both) during the long-, but not the short-, segment infusion. By contrast, increases in plasma CCK and GIP did not differ between days. The rises in blood glucose and plasma insulin were greater during the long-than during the short-segment infusion (P Ͻ 0.05). During the long-but not the short-segment infusion, antral pressure waves (PWs) were suppressed (P Ͻ 0.05). Isolated pyloric PWs and basal pyloric pressure were stimulated on both days. In conclusion, the release of GLP-1 and ghrelin, but not CCK and GIP, is dependent upon Ͼ60 cm of the intestine being exposed to glucose.gastrointestinal hormone secretion; antropyloric motility; small intestinal nutrient exposure; glucagon-like peptide-1; glucose-dependent insulinotropic peptide; cholecystokinin THE KNOWN REGULATORY GUT PEPTIDES have differing distributions along the small intestine. For example, GIP is secreted from endocrine K cells (7) and CCK by endocrine I cells (33) in the proximal small intestine, whereas peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) are secreted from endocrine L cells in the distal small intestine (6, 28). Whether these peptides are released primarily, or exclusively, by direct local contact with specific nutrients in their regions of storage or are released reflexively from the distal small intestine by signals arising from the proximal small intestine, or vice versa, is still debatable. For example, in rats, intravenous infusion of GIP has been shown to stimulate the secretion of GLP-1 (34). In dogs, Lin and colleagues (18,19) demonstrated that cholecystokinin (CCK) was released equipotently whether fat contacted the proximal, or distal, small intestine and that the release of PYY was dependent, at least in part, on the stimulation of CCK by fat confined to proximal small intestine. On the other hand, Pilichiewicz et al. (31) concluded recently that, in humans, CCK was released only by fat in the proximal small intestine and PYY was much more potently released by fat locally in the distal small intestine than in the jejunum. These last observations suggest that the nutrient-stimulat...

Effect of the glycemic index of carbohydrates on day-long (10 h) profiles of plasma glucose, insulin, cholecystokinin and ghrelin

“…However, GHR production is partly mediated by lower intestinal osmolarity and insulin concentrations, not just the presence of nutrients in the stomach or duodenum (Cummings, 2006). Indeed, we found that GHR and insulin concentrations were inversely correlated, purporting previous findings for a role of insulin in the prandial suppression of GHR (Blom et al, 2005;Little et al, 2006). It has also been suggested that GHR may play a role in the adipocyte regulation of glucose homoeostasis through the direct potentiation of insulin-stimulated glucose uptake (Patel et al, 2006).…”

“…Mourot et al (Mourot et al, 1988) demonstrated an inverse relationship between gastric emptying half-time and the magnitude of the glycemic response to four foods: potatoes, bread, rice and spaghetti. In this study, the higher profile of CCK on the low GI diet may therefore be attributable to a slower rate of gastric emptying and hence entry of carbohydrate and other macronutrients into the proximal small intestine (o60 cm (Little et al, 2006)). This may prolong stimulation of I cells, which in turn may further decrease gastric emptying and maintain higher CCK production.…”

“…GHR concentrations increase preprandially and decrease postprandially (Cummings et al, 2001), particularly after carbohydrate-rich meals (Erdmann et al, 2004;Overduin et al, 2005). In some studies, GHR concentrations are inversely correlated to insulin concentrations (Blom et al, 2005;Little et al, 2006).…”

Targeting the gastrointestinal tract to treat type 2 diabetes

“…In the traditional view, the proximal intestine contains I-cells, which secrete CCK, and GIP-releasing K-cells, while L-cells cosecrete PYY and GLP-1 and are located mainly in the distal intestine (Little et al 2006). However, recent work has challenged these classical views, as individual enteroendocrine cells have been shown to express a variety of gut peptides (Egerod et al 2012, Grunddal et al 2016, while the proximal small intestine has been shown to secrete significant amounts of GLP-1 (Theodorakis et al 2006).…”

Short-Bowel Syndrome in Children — An Update in Management Strategies

“…Additionally, colon resection results in further depletion of energy as studies have shown that the colon can absorb up to 15% of energy requirements [40][41]. Furthermore, patients with end-jejunostomy display increased gastric emptying and intestinal transportation [42] due to the lack of the protective effect of hormonal mediators such as GLP-1 GLP-2, and peptide YY [23]. Studies in adults have shown that the presence of little or no colon and less than 50-100 cm of jejunum results in permanent parenteral nutrition [43,44].…”